摘要
目的 探讨神经纤毛及唾样蛋白2(NETO2)在口腔鳞状细胞癌(OSCC)中的临床意义,及其敲低对OSCC细胞增殖、迁移和侵袭的影响。方法 使用基因表达谱交互分析(GEPIA)分析OSCC患者的癌组织和非癌组织中NETO2表达,并分析NETO2表达与OSCC患者总生存率的相关性。于2020年11月至2022年1月从广西科技大学第二附属医院获得124份癌标本及配对正常组织(距肿瘤边缘5 cm)。通过蛋白质印迹法分析NETO2表达。在体外实验中,实验1将HSC-4细胞分为NETO2敲低(sh1、sh2)组和相应对照(NC)组;实验2将HSC-4细胞分为NETO2敲低(sh1、sh1+EGF)组和相应对照(NC)组。使用CCK-8、克隆形成和Transwell分析研究NETO2敲低对HSC-4细胞增殖、侵袭和迁移的影响。此外,在NETO2敲低的HSC-4细胞中加入ERK激动剂(EGF)进行拯救实验。结果 NETO2在OSCC组织中的表达异常高,并且NETO2高表达OSCC患者的预后较差。与NC组相比,sh1组和sh2组的细胞活力、集落形成能力、迁移和侵袭细胞数均显著降低(P<0.05)。基因本体论(GO)的基因集富集分析(GSEA)揭示了OSCC细胞中NETO2的敲低导致ERK信号通路基因表达的显著变化。与sh1组相比,sh1+EGF组增加了NETO2敲低细胞中ERK的表达(P<0.05)。此外,sh1+EGF组的NETO2敲低OSCC细胞的生长、集落形成能力、迁移和侵袭均显著高于sh1组(P<0.05)。结论 OSCC组织中高水平的NETO2表达与患者的不良预后相关。NETO2是一种重要的癌蛋白,可能激活ERK信号通路以促进OSCC细胞的增殖、侵袭和转移。
Objective To investigate the clinical significance of neuropilin and tolloid-like 2(NETO2)in oral squamous cell carcinoma(OSCC)and the effect of its knockdown on OSCC cell proliferation,migration and invasion.Methods NETO2 expression in OSCC and non-OSCC tissues of OSCC patients was analyzed using Gene Expression Profile Interaction Analysis(GEPIA),and the correlation of NETO2 expression with overall survival in OSCC patients was analyzed.From November 2020 to January 2022,124 cancer specimens and matched normal tissues(5cm from the tumor edge)were obtained from our hospital.NETO2 expression was analyzed by Western blotting.In in vitro experiments,HSC-4 cells were divided into NETO2 knockdown(sh1,sh2)group and corresponding control(NC)group.The effects of NETO2 on HSC-4 cell proliferation,invasion and migration were investigated using CCK-8,clone formation and Transwell assays.In addition,rescue experiments were performed by adding an ERK agonist(EGF)to NETO2-knockdown HSC-4 cells.Results The expression of NETO2 in OSCC tissues was abnormally high,and the prognosis of OSCC patients with high NETO2 expression was poor.Compared with the NC group,the cell viability,colony-forming ability,and the number of migrating and invasive cells in the sh1 and sh2 groups were significantly decreased(P<0.05).Gene Set Enrichment Analysis(GSEA)of Gene Ontology(GO)revealed that knockdown of NETO2 in OSCC cells resulted in significant changes in ERK signaling pathway gene expression.Compared with sh1 group,sh1+EGF group increased the expression of ERK in NETO2 knockdown cells(P<0.05).In addition,the growth,colony formation ability,migration and invasion of NETO2 knockdown OSCC cells in the sh1+EGF group were significantly higher than those in the sh1 group(P<0.05).Conclusion High levels of NETO2 expression in OSCC tissues are associated with poor patient outcomes.NETO2 is an important oncoprotein that may activate the ERK signaling pathway to promote the proliferation,invasion and metastasis of OSCC cells.
作者
陆珣珣
韦曙平
韦富贵
LU Xun-xun;WEI Shu-ping;WEI Fu-gui(Department of Otolaryngology,Head and Neck Surgery,The Second Affiliated Hospital of Guangxi University of Science and Technology,Liuzhou 545006,Guangxi,China)
出处
《广东医学》
CAS
2023年第10期1223-1229,共7页
Guangdong Medical Journal
基金
广西壮族自治区卫生健康委员会自筹经费科研课题(Z-B20220958)。
关键词
神经纤毛及唾样蛋白2
口腔鳞状细胞癌
ERK通路
增殖
转移
neuropilin and tolloid-like 2
oral squamous cell carcinoma
ERK pathway
proliferation
metastasis
